UPDATE ON RETINOPATHY OF PREMATURITY

Editor's Note: I want to thank Johns Hopkins
for introducing me to Dr. Michael Repka, and Dr.
Repka for submitting this highly informative article
on a very timely subject. It is also our good fortune
that Dr. Repka has expressed an interest in submitting
additional articles to Future Reflections. If
there is a particular medical topic you would like
to suggest to Dr. Repka, please write to: Barbara
Cheadle, Editor, Future Reflections, 1800
Johnson Street, Baltimore, MD 21230. Topics
should, of course, be related in some way to eye diseases
and conditions of the eye.

Retinopathy of prematurity or ROP affects an estimated
2,100 infants each year in the United
States. These children may lose vision entirely,
or be left partially sighted.

ROP, formerly known as retrolental fibroplasia
or RLF, was first observed in the early 1940's. At
its initial appearance it was often confused with
an ocular tumor. At that time ROP was recognized
only in the most advanced form in which
the eye was very damaged. Research during the
1940's and early 50's led to the discovery that
oxygen caused ROP. By restricting the use of
oxygen, retinopathy of prematurity virtually
ceased to occur by the mid-1950's. The patients
affected by retinopathy of prematurity during the
1940's and 1950's were older and bigger than the
patients who are developing retinopathy of
prematurity today.

During the 1960's, 70's, and 80's, medicine's
ability to support low birth weight babies has improved.
This has produced a dramatically increased
survival rate for infants with birth
weights less than one kilogram (2 pounds, 3 ounces).
For example, in 1950 only 8% of babies
born with this birth weight survived. By 1980 the figure had reached 35%, and by 1990 the figure
is likely to be 70% for many neonatal intensive
care units. This improved survival rate has been
paralleled by a dramatic increase in the number
of children with retinopathy of prematurity.
Retinopathy of prematurity most frequently affects
the eyes of infants with birth weights less
than 1,250 grams (2 pounds, 12 ounces), especially
those infants with multiple medical problems.
The cause of retinopathy of prematurity no
longer appears to be simply excessive oxygen.
Vitamin A and E deficiencies have been implicated.
Low oxygen and high carbon dioxide
blood levels, high acid concentration in the
blood, low bilirubin, and other metabolic factors
appear to play a role in the development of this
disease. This has led to investigation of multiple
therapies to reduce the incidence of the disease.
Many hypotheses of causation still include
oxygen as the ultimate cause of damage.

In the premature newborn, retinal blood vessels
do yet not extend throughout the retina. The
growing tips of these bloodvessels are responsive
to changes in the body. These vessels respond to
insult by exuberant growth, which is called
proliferative disease. About 5% of small infants
(1,250 grams) will develop a significant amount
of proliferation. Once these abnormal blood
vessels are present, they may completely disappear,
or less commonly, proliferate further leading
to scarring of the retina, and in some cases
retinal detachment. If this proliferative change
could be stopped, the scarring manifestations of
the disease would not occur. Early trials of laser
treatment in Japan and laser or freezing
(cryotherapy) treatments in the United States
showed promise for stopping the disease. Multiple
small studies done since that time seemed to
confirm that the proliferative changes could be
completely aborted or caused to regress if a portion
of the retina could be treated. Because of
the relative ease of performing freezing treatments,
babies today are treated with cryotherapy.

Cryotherapy involves a series of approximately
35 freezing applications to the outside portion of
the retina, an area not used for vision. The treatment
is done with local anesthesia. Drops are
used for a few days postoperatively. The National
Trial of Cryotherapy for Retinopathy of
Prematurity, sponsored by the National Institutes
of Health, evaluated the effect of
cryotherapy when applied to patients most at risk
for the scarring changes of retinopathy of
prematurity. Only one eye of each patient was
treated because there was concern about the
short-term and long-term complications of this
treatment, including loss of the eye. Of the untreated
eyes, 43% of eyes had an unfavorable outcome.
Such patients would not ever develop
good central vision. On the other hand, for the
treated eyes, only 22% developed an unfavorable
visual outcome. There are therefore three important
lessons from this study. 1) Only 5% of all
babies born at risk for retinopathy of prematurity
will develop the disease severely enough to warrant
the application of cryotherapy. 2) Of those
patients, one of five will still develop the scarring
changes of retinopathy of prematurity. 3) Cryotherapy does not eliminate the chance of
poor vision, hut only reduces its frequency.

Cryotherapy is not the final solution for this disease.
Research must continue into exploring
other ways to try and prevent the proliferative
retinal changes from occurring. Some promising
avenues of research include the extension of
freezing treatments to less involved patients and
earlier treatment in an attempt to further reduce
the number of children who will have visual loss
from retinopathy of prematurity. Research into
metabolic and vitamin abnormalities continue.

ADVANCED DISEASE

Once retinal detachment or scarring has
developed there are technical difficulties in treating the retina. Though extensive vitreous
and retinal surgery has been successful in some
cases, there is rarely restoration of functional
vision for these treated eyes. Currently being initiated
is a multi-center investigation into the
early management of retinopathy of prematurity
that has been complicated by a retinal detachment.
Results from the study will take years to accumulate.

LONG
TERM PROBLEMS

Premature children who develop mild or advanced
forms of retinopathy of prematurity are
at increased risk for multiple ophthalmologic
problems. These include strabismus or squint;
amblyopia (lazy eye); and high levels of refractive
error (need for glasses), particularly nearsightedness.
The long-term complications include
retinal detachments occurring in infancy
and young adulthood, as well as narrow angle
glaucoma, a type of glaucoma rarely seen in
young patients without retinopathy of
prematurity in their background. Consequently,
all patients, even those with markedly diminished
vision, should continue to be monitored by an
ophthalmologist for these ocular problems.